safety study of recombinant vaccinia virus administered intravenously in patients with metastatic, refractory colorectal carcinoma

Conditions: Carcinoma, Colorectal

Summary: the purpose of this pilot safety study is to evaluate the safety and tolerability of jx-594 (pexa-vec) administered intravenously every 2 weeks in colorectal carcinoma patients who are refractory to or intolerant of oxaliplatin, irinotecan, and erbitux treatments.


Eligibility criteria:
inclusion criteria: * histologically-confirmed, advanced/metastatic colorectal carcinoma * failed both oxaliplatin and irinotecan based regimens for advanced/metastatic disease (if tumor advanced either immediately or within 3 months of the end of treatment) * resistance to erbitux: patients with ras mutations, or for whom erbitux has failed (if tumor advanced either immediately or within 3 months of the end of treatment, or there is no response to erbitux therapy due to a lack of expression of egfr (epidermal growth factor)) * karnofsky performance score (kps) ≥ 70 * age ≥18 years * laboratory safety: wbc ≥ 3,500 cells/mm3 and ≤ 50,000 cells/mm3, anc ≥ 1,500 cells/mm3, hemoglobin ≥ 10 g/dl (transfusion allowed), platelet count ≥ 100,000 plts/mm3,total bilirubin ≤ 1.5 x uln, inr ≤ 1.5, ast, alt ≤ 2.5x uln (in case of liver metastasis: ast,alt ≤5.0 x uln) * serum chemistries within normal limits (wnl) or grade 1 (excluding alkaline phosphatase) - if patients are diabetic, a fasting glucose must be done and patients must be \> 160 mg/dl. * patients who, if they are sexually active, are willing and able to refrain from sexual activity for 3 weeks following jx-594 administration. patients who are willing and able to use a permitted contraceptive for 3 months after the final administration of jx-594. exclusion criteria: * significant immunodeficiency due to underlying illness (e.g. hiv/aids) and/or medication (e.g. systemic corticosteroids) * known myeloproliferative disorders requiring systemic therapy * history of exfoliative skin condition (e.g. eczema or ectopic dermatitis) requiring systemic therapy * history of acquiring opportunistic infections. * tumor(s) invading a major vascular structure (e.g. carotid artery) * tumor(s) in location that would potentially result in significant clinical adverse effects if post-treatment tumor swelling were to occur * clinically uncontrolled and/or rapidly accumulating ascites, pericardial and/or pleural effusions * history of severe or unstable cardiac disease * current, known cns malignancy (history of completely resected or irradiated brain metastases by wbrt or stereotactic radiosurgery allowed) * administered anti-cancer therapy within 4 weeks prior to first treatment (6 weeks in case of mitomycin c or nitrosoureas) * use of anti-viral, anti-platelet, or anti-coagulation medication \[patients who discontinue such medications within 7 days prior to first treatment may be eligible for this study.\] low dose aspirin (approximately 81 mg) allowed. * pulse oximetry o2 saturation \<90% pulse oximetry o2 saturation \<90% at rest * experienced a severe systemic reaction or side-effect as a result of a previous smallpox vaccination * pregnant or nursing * household contact exclusions: * women who are pregnant or nursing an infant * children \< 5 years old * people with skin disease (e.g. eczema, atopic dermatitis, and related diseases * immunocompromised hosts (severe deficiencies in cell-mediated immunity, including aids, organ transplant recipients, hematologic malignancies)

Keywords: vaccinia vaccinia virus jx-594 jennerex colorectal carcinoma colorectal cancer colon cancer rectal cancer pexa-vec